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Chronic kidney disease (CKD) impacts about 1 in 7 adults in the United States, but African Americans (AAs) carry a disproportionately higher burden of disease. Epigenetic modifications, such as DNA methylation at cytosine-phosphate-guanine (CpG) sites, have been linked to kidney function and may have clinical utility in predicting the risk of CKD. Given the dynamic relationship between the epigenome, environment, and disease, AAs may be especially sensitive to environment-driven methylation alterations. Moreover, risk models incorporating CpG methylation have been shown to predict disease across multiple racial groups. In this study, we developed a methylation risk score (MRS) for CKD in cohorts of AAs. We selected nine CpG sites that were previously reported to be associated with estimated glomerular filtration rate (eGFR) in epigenome-wide association studies to construct a MRS in the Hypertension Genetic Epidemiology Network (HyperGEN). In logistic mixed models, the MRS was significantly associated with prevalent CKD and was robust to multiple sensitivity analyses, including CKD risk factors. There was modest replication in validation cohorts. In summary, we demonstrated that an eGFR-based CpG score is an independent predictor of prevalent CKD, suggesting that MRS should be further investigated for clinical utility in evaluating CKD risk and progression.

BackgroundPatients with chronic kidney disease (CKD) face risks of not only end-stage kidney disease (ESKD), cardiovascular disease (CVD) and death, but also decline in kidney function, quality of life (QOL) and mental and physical well-being. This study describes the multidimensional trajectories of CKD using clinical events, kidney function and patient-reported outcome measures (PROMs). We hypothesized that more advanced CKD stages would associate with more rapid decline in each outcome.MethodsAmong 3939 participants enrolled in the Chronic Renal Insufficiency Cohort (CRIC) Study, we evaluated multidimensional disease trajectories by G- and A-stages of enrollment estimated glomerular filtration rate (eGFR) and albuminuria, respectively. These trajectories included clinical events (ESKD, CVD, heart failure and death), eGFR decline and PROMs [kidney disease QOL (KDQOL) burden, effects and symptoms questionnaires, as well as the 12-item short form mental and physical component summaries]. We also evaluated a group-based multitrajectory model to group participants on the basis of longitudinal PROMs and compared group assignments by enrollment G- and A-stage.ResultsThe mean participant age was 58 years, 45% were women, mean baseline eGFR was 44 mL/min/1.73 m2 and median urine albumin:creatinine ratio was 52 mg/g. The incidence of all clinical events was greater and eGFR decline was faster with more advanced G- and A-stages. While baseline KDQOL and physical component measures were lower with more advanced G- and A-stage of CKD, changes in PROMs were inconsistently related to the baseline CKD stage. Groups formed on PROM trajectories were fairly distinct from existing CKD staging (observed agreement 60.6%) and were associated with the risk of ESKD, CVD, heart failure and death.ConclusionsMore advanced baseline CKD stage was associated with a higher risk of clinical events and faster eGFR decline, and was only weakly related to changes in patient-reported metrics over time.

IntroductionManagement of chronic kidney disease (CKD) entails high medical complexity and often results in high hospitalization burden. There are limited data on the associations of longitudinal hospital utilization patterns with adverse clinical outcomes in individuals with CKD.MethodsWe derived cumulative all-cause hospitalization trajectory groups using latent class trajectory analysis in 3012 participants of the Chronic Renal Insufficiency Cohort (CRIC) Study who were alive and did not reach end-stage kidney disease (ESKD) within 4 years of study entry. Cox proportional hazards models tested the associations between hospitalization trajectory groups and risks of ESKD and death prior to the onset of ESKD (ESKD-censored death).ResultsWithin 4 years of study entry, there were 5658 hospitalizations among 3012 participants. We identified 3 distinct subgroups of individuals with CKD based on cumulative all-cause hospitalization trajectories over 4 years: low-utilizer (n = 1066), intermediate-utilizer (n = 1802), and high-utilizer (n = 144). High-utilizers represented a patient population of lower socioeconomic status who had a greater prevalence of comorbid conditions and lower kidney function compared with intermediate- and low-utilizers. After the 4-year ascertainment period to form the trajectory subgroups, there were 544 ESKD events and 437 ESKD-censored deaths during a median follow-up time of 5.1 years. Compared with low-utilizers, intermediate-utilizers and high-utilizers were at 1.49-fold (95% confidence interval [CI] 1.22-1.84) and 1.75-fold (95% CI 1.20-2.56) higher risk of ESKD in adjusted analyses, respectively. Compared with low-utilizers, intermediate-utilizers and high-utilizers were at 1.48-fold (95% CI 1.17-1.87) and 2.58-fold (95% CI 1.74-3.83) higher risk of ESKD-censored death in adjusted analyses, respectively.ConclusionsTrajectories of cumulative all-cause hospitalization identify subgroups of individuals with CKD who are at high risk of ESKD and death.

BackgroundPreparedness regarding prognosis and treatment options enables patients to cope with uncertainties, make value-based treatment decisions, and set treatment goals. Yet, little is known about the expectedness of end-stage kidney disease (ESKD) patients' treatment experiences beyond their desire for better treatment education.ObjectiveTo describe unexpected adverse treatment experiences among ESKD patients.MethodThe authors conducted 7 focus groups with 55 dialysis patients and living-donor kidney transplantation recipients receiving medical care in Baltimore, Maryland. Data were analyzed thematically. Themes present in different treatment groups were highlighted to provide insight into common experiences.ResultsThe authors identified 5 themes: (1) psychological reactions, (2) constrained freedom of choice, (3) treatment delivery and logistics, (4) morbidity, and (5) finances.ConclusionPatients were unprepared for nonclinical, logistical, and clinical aspects of ESKD treatment. The need for providers' use of tailored preparatory techniques and the development of pretreatment interventions to help patients know what to expect from and feel psychologically prepared for treatment, particularly with respect to nonclinical implications, is critical. These efforts have great potential to improve patients' treatment experiences.

BackgroundUse of routine medical care (RMC) is advocated to address ethnic/racial disparities in chronic kidney disease (CKD) risks, but use is less frequent among African Americans. Factors associated with low RMC use among African Americans at risk of renal outcomes have not been well studied.MethodsWe examined sociodemographic, comorbidity, healthcare access, and psychosocial (discrimination, anger, stress, trust) factors associated with low RMC use in a cross-sectional study. Low RMC use was defined as lack of a physical exam within one year among participants with CKD (estimated glomerular filtration rate  30 mg/g) or CKD risk factors (diabetes or hypertension). We used multivariable logistic regression to estimate the odds of low RMC use at baseline (2000-2004) for several risk factors.ResultsAmong 3191 participants with CKD, diabetes, or hypertension, 2024 (63.4%) were ≥ 55 years of age, and 700 (21.9%) reported low RMC use. After multivariable adjustment, age

BackgroundGiven the high prevalence of chronic kidney disease (CKD), primary care physicians (PCPs) frequently manage early stage CKD. Nonetheless, there are challenges in providing optimal CKD care in the primary care setting. This study sought to understand PCPs' perceptions of barriers and facilitators to the optimal management of CKD.Study designMixed methods study.Settings and participantsCommunity-based PCPs in four US cities: Baltimore, MD; St. Louis, MO; Raleigh, NC and San Francisco, CA.MethodologyWe used a self-administered questionnaire and conducted 4 focus groups of PCPs (n = 8 PCPs/focus group) in each city to identify key barriers and facilitators to management of patients with CKD in primary care.Analytic approachWe conducted descriptive analyses of the survey data. Major themes were identified from audio-recorded interviews that were transcribed and coded by the research team.ResultsOf 32 participating PCPs, 31 (97%) had been in practice for >10 years, and 29 (91%) practiced in a non-academic setting. PCPs identified multiple barriers to managing CKD in primary care including at the level of the patient (e.g., low awareness of CKD, poor adherence to treatment recommendations), the provider (e.g., staying current with CKD guidelines), and the health care system (e.g., inflexible electronic medical record, limited time and resources). PCPs desired electronic prompts and lab decision support, concise guidelines, and healthcare financing reform to improve CKD care.ConclusionsPCPs face substantial but modifiable barriers in providing care to patients with CKD. Interventions that address these barriers and promote facilitative tools may improve PCPs' effectiveness and capacity to care for patients with CKD.

Few investigations have evaluated the incremental usefulness of tubular injury biomarkers for improved prediction of chronic kidney disease (CKD) progression. As such, we measured urinary kidney injury molecule-1, neutrophil gelatinase-associated lipocalin, N-acetyl-ß-D-glucosaminidase and liver fatty acid binding protein under highly standardized conditions among 2466 enrollees of the prospective Chronic Renal Insufficiency Cohort Study. During 9433 person-years of follow-up, there were 581 cases of CKD progression defined as incident end-stage renal disease or halving of the estimated glomerular filtration rate. Levels of the urine injury biomarkers, normalized for urine creatinine, were strongly associated with CKD progression in unadjusted Cox proportional hazard models with hazard ratios in the range of 7 to 15 comparing the highest with the lowest quintiles. However, after controlling for the serum creatinine-based estimated glomerular filtration rate and urinary albumin/creatinine ratio, none of the normalized biomarkers was independently associated with CKD progression. None of the biomarkers improved on the high (0.89) C-statistic for the base clinical model. Thus, among patients with CKD, risk prediction with a clinical model that includes the serum creatinine-based estimated glomerular filtration rate and the urinary albumin/creatinine ratio is not improved on with the addition of renal tubular injury biomarkers.